4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid has retinoid activity, and its use as an active ingredient of a medicament has been expected. Conventionally, this compound is known to exist at least as two kinds of crystal polymorphs, that is, (1) a crystal melting at 193° C. and (2) a crystal melting at 233° C. [see, Japanese Patent No. 3001632 as for (1), and Japanese Patent Unexamined Publication (Kokai) No. 61-76440 as for (2). (3) A crystal melting at 205.5° C. to 206.5° C. is disclosed in Chem. Pharm. Bull., 32, p.4209, 1984. However, this crystal was later reported to actually have the melting point of 231° C. to 232° C. and thus revealed to be identical to the crystal (2) (J. Cellular Physiology, 135, pp.179-188, 1988)].
The crystal described in Japanese Patent No. 3001632, which melts at 193° C., is prepared by using a mixture of methanol and water as a recrystallization solvent. The crystal that melts at 233° C. is prepared by using a mixture of ethyl acetate and hexane as a recrystallization solvent. The latter crystal (melting point: 233° C.) contains 1200 ppm and 190 ppm of residual ethyl acetate and hexane, respectively, and thus has a problem that the crystal can hardly satisfy the standard values of residual solvents provided by the Ministry of Health and Welfare (ethyl acetate: 5000 ppm or less; hexane: 290 ppm). Whilst, the crystal that melts at 193° C. has a characteristic feature that a residual methanol level can be significantly lowered.
However, the crystal that melts at 193° C. has a problem that the crystalline form readily occurs transition by physical impact, and thus preparation thereof as a uniform crystal is extremely difficult. Accordingly, this crystal lacks an aptitude as a raw material for large scale manufacture of a pharmaceutical product that constantly meets quality standard. Whilst the crystal that melts at 233° C. has been revealed to have high stability against physical impact, as well as against heat, temperature, light and the like. However, a method for selective preparation of this crystal has not been known so far. Further, a method is known for preparation of the crystal that melts at 233° C. in which a mixture of ethyl acetate and hexane are used as a recrystallization solvent. However, hexane is classified as Class 2 solvent according to the guidelines for residual solvents of pharmaceutical products, and is undesirable solvent to be remained in pharmaceutical preparations. Accordingly, a crystal is strongly desired that does not contain hexane as a residual solvent.